Acrodermatitis Enteropathica

NORD gratefully acknowledges John McGrath, MD, St John's Institute of Dermatology, Guy's Hospital, London, for assistance in the preparation of this report.

Synonyms of Acrodermatitis Enteropathica

AE

Brandt syndrome

Danbolt-Cross syndrome

zinc deficiency, congenital

General Discussion

Acrodermatitis enteropathica (AE) is a disorder of zinc metabolism that occurs in one of three forms: an inborn (congenital) form and two acquired forms. The inborn form of AE is a rare genetic disorder characterized by intestinal abnormalities that lead to the inability to absorb zinc from the intestine. The lack of zinc presents, characteristically, as: (1) skin inflammation with pimples (pustular dermatitis) occurring around the mouth and/or anus, (2) diarrhea, and (3) abnormal nails (nail dystrophy). In the acute phase, irritability and emotional disturbances are evident due to wasting (atrophy) of the brain cortex. It is important to recognize and treat this disorder.
The acquired form of this disorder generates similar symptoms. One transient form can result from failure of the mother to secrete zinc into her breast milk. Other acquired forms of AE sometimes result after surgery to bypass some of the upper intestine or from special intravenous nutritional programs that are prepared without the appropriate amount of zinc.
Supplemental zinc usually eliminates the symptoms.

Signs & Symptoms

Acrodermatitis enteropathica is characterized by chronic diarrhea which may be mild or severe, and the presence of fatty substances in the feces (steatorrhea). In the congenital form symptoms start gradually, frequently at the time of weaning of an infant. The skin around body openings such as the mouth, anus, and eyes, and the skin on elbows, knees, hands, and feet become inflamed. Skin lesions are usually blistered (vesicobullous) and after drying out become psoriasis-like. The skin around the nails may also be inflamed and the nail may be abnormal due to malnourished tissue. Hair loss on the scalp, eyelids, and eyebrows may be total (alopecia). Inflammation of the membrane that lines the eyelid (conjunctivitis), usually also occurs.

The blood zinc level in people with the congenital form of this disorder is abnormally low, although rarely normal blood zinc levels have also been observed.

A separate type of transient zinc deficiency in infants can result from a different congenital abnormality – but one which is not in the infant but rather in the mother. Notably in some lactating women, a zinc-binding factor produced by the pancreas and present in human milk may be lacking. Breast-fed infants of these women may also develop lowered blood levels of zinc with other symptoms of this disorder, because the milk is deficient in the proper amount of the zinc- binding factor. Once an alternative source of oral zinc is introduced into the infant’s diet (e.g. formula milk) the zinc deficiency rectifies and the infant is cured.

With treatment, all patients with acrodermatitis enteropathica can lead normal lives.

Frequently, long remissions may occur, usually starting during puberty. However, in rare cases, women may have a recurrence of the disorder during pregnancy and increased zinc supplementation may be necessary.

Causes

The congenital form of acrodermatitis enteropathica is transmitted as an autosomal recessive genetic disorder. It appears to be the result of mutations in the SLC39A4 gene.

Genetic diseases are determined by a combination of genes for a particular trait that are on the chromosomes received from the father and the mother.

Recessive genetic disorders occur when an individual inherits the same abnormal gene for the same trait from each parent. If an individual receives one normal gene and one gene for the disease, the person will be a carrier for the disease, but usually will not show symptoms. The risk for two carrier parents to both pass the defective gene and, therefore, have an affected child is 25% with each pregnancy. The risk to have a child who is a carrier like the parents is 50% with each pregnancy. The chance for a child to receive normal genes from both parents and be genetically normal for that particular trait is 25%. The risk is the same for males and females.

All individuals carry a few abnormal genes. Parents who are close relatives (consanguineous) have a higher chance than unrelated parents to both carry the same abnormal gene, which increases the risk to have children with a recessive genetic disorder.

Some women fail to generate adequate zinc levels in their breast milk – and that can also have a genetic cause. A single mutation in the SLC30A2 mutation can reduce breast milk zinc. This tendency does not require two gene abnormalities, one is sufficient and people who have this condition have a 50% chance of passing it on to their offspring.

Affected Populations

The congenital form of arodermatitis enteropathica is a rare disorder beginning during infancy. The incidence is about 1 in 500,000 births and the condition affects males and females in equal numbers. Healthy breast-fed infants of female patients with the disorder can also become affected. The acquired form of AE is rare because in recent years zinc supplements have been added to the parenteral nutrition regimen, although acquired forms are more common in some regions such as Southeast Asia and sub-Saharan Africa where gastro-intestinal malabsorption syndrome are more frequent.

Related Disorders

Symptoms of the following disorder can be similar to those of acrodermatitis enteropathica. Comparisons may be useful for a differential diagnosis:

Celiac sprue (gluten enteropathy) is a chronic, hereditary, intestinal malabsorption disorder caused by intolerance to dietary gluten. The illness is characterized by a flat mucous lining of the jejunum (part of the small intestine). Symptoms include weight loss, chronic diarrhea, abdominal cramping and bloating, intestinal gas, and muscle wasting. Clinical and/or histologic improvement of symptoms, follow withdrawal of dietary gluten. (For more information on this disorder, choose “Celiac Sprue” as your search term in the Rare Disease Database.)

Standard Therapies

Acrodermatitis enteropathica is treated with zinc supplements in the form of zinc sulfate. These supplements should be given as soon as diagnosis of the disorder is made and they have to be continued for life. The drug Diodoquin (iodoquinol) is another treatment that usually clears up symptoms within a week. If the disorder is caused by intravenous feeding, adding zinc supplements to the nutritional regimen can prevent and/or clear up manifestations of AE.

Genetic counseling is recommended for families of patients with the congenital form of acrodermatitis enteropathica.

Investigational Therapies

Information on current clinical trials is posted on the Internet at www.clinicaltrials.gov. All studies receiving U.S. government funding, and some supported by private industry, are posted on this government website.

For information about clinical trials being conducted at the National Institutes of Health (NIH) in Bethesda, MD, contact the NIH Patient Recruitment Office:

Years Published

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